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Front. Endocrinol. | doi: 10.3389/fendo.2019.00705

Melanocortin-4 Receptor in Spotted Sea Bass, Lateolabrax maculatus: Cloning, Tissue Distribution, Physiology, and Pharmacology

 Kai-Qiang Zhang1, 2,  Zhi-Shuai Hou3,  Hai-Shen Wen1, 2,  Yun Li1, 2*,  Xin Qi2, Wen-Juan Li2 and Ya-Xiong Tao3
  • 1Ocean University of China, China
  • 2Key Laboratory of Marine Aquaculture Ministry of Education, Ocean University of China, China
  • 3Department of Anatomy, Physiology and Pharmacology, College of Veterinary Medicine, Auburn University, United States

Melanocortin-4 receptor (MC4R) plays important roles in regulation of multiple physiological processes including energy homeostasis, reproduction, sexual function and other functions in mammals. Recent studies suggested that teleost MC4Rs have different physiological functions and pharmacological characteristics when compared to mammalian MC4Rs. In this study, we investigated spotted sea bass (Lateolabrax maculatus) MC4R (LmMC4R) physiology and pharmacology. Spotted sea bass mc4r consisted of a 984 bp open reading frame encoding a protein of 327 amino acids. LmMC4R was homologous to those of several teleost MC4Rs and human MC4R (hMC4R). qRT-PCR and in situ hybridization revealed that mc4r transcripts were highly expressed in the brain, followed by pituitary and liver. Brain mc4r transcripts were down-regulated in long-term and short-term fasting challenges. LmMC4R was a functional receptor with lower maximal binding and higher basal activity than hMC4R. THIQ was not able to displace 125I-NDP-MSH but could affect intracellular cAMP accumulation, suggesting that they were allosteric ligands for LmMC4R. In vitro studies with spotted sea bass brain cells indicated that mRNA levels of neuropeptide Y, Agouti-related peptide and growth hormone were down-regulated by -MSH. In summary, we cloned spotted sea bass MC4R, and showed that it had different pharmacological properties compared to hMC4R, and potentially different functions.

Keywords: Spotted sea bass, melanocortin-4 receptor, signaling, allosteric modulator, constitutive activity

Received: 07 May 2019; Accepted: 30 Sep 2019.

Copyright: © 2019 Zhang, Hou, Wen, Li, Qi, Li and Tao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Yun Li, Ocean University of China, Qingdao, China, yunli0116@ouc.edu.cn